Lloyd, E. C. | Search bioRxiv

bioRxiv2021

Large-scale exploration of whole-brain structural connectivity in anorexia nervosa: alterations in the connectivity of frontal and subcortical networks

BackgroundAnorexia nervosa (AN) is characterized by disturbances in cognition and behavior surrounding eating and weight. The severity of AN combined with the absence of localized brain abnormalities suggests distributed, systemic underpinnings that may be identified using diffusion-weighted MRI (dMRI) and tractography to reconstruct white matter pathways. MethodsdMRI data acquired from female patients with AN (n = 147) and female healthy controls (HC; n = 119), aged 12-40 years, were combined across five studies. Probabilistic tractography was completed, and full cortex connectomes describing streamline counts between 84 brain regions generated and harmonized. Graph theory methods were used to describe alterations in network organization in AN. The network-based statistic tested between-group differences in brain subnetwork connectivity. The metrics strength and efficiency indexed the connectivity of brain regions (network nodes), and were compared between groups using multiple linear regression. ResultsIndividuals with AN, relative to HC, had reduced connectivity in a network comprising subcortical regions and greater connectivity between frontal cortical regions (p < 0.05, FWE corrected). Node-based analyses indicated reduced connectivity of the left hippocampus in patients relative to HC (p < 0.05, permutation corrected). Severity of illness, assessed by BMI, was associated with subcortical connectivity (p < 0.05, uncorrected). ConclusionsAnalyses identified reduced structural connectivity of subcortical networks and regions, and stronger cortical network connectivity, amongst individuals with AN relative to HC. These findings are consistent with alterations in feeding, emotion and executive control circuits in AN, and may direct hypothesis-driven research into mechanisms of persistent restrictive eating behavior.

neuroscience↗

bioRxiv2018

Bidirectional effects of anxiety and anorexia nervosa: A Mendelian randomization study

ObjectivesTo assess bidirectional effects of anxiety and anorexia nervosa (AN) phenotypes. Design Two-sample Mendelian randomization.\n\nSettingGenome-wide association study (GWAS) summary statistics from the Psychiatric Genomics Consortium (PGC), analysis of the UK Biobank sample, and Anxiety Neuro Genetics Study (ANGST) consortium.\n\nParticipantsEuropean descent participants from the PGC (n = 14,477), UK Biobank (n = 348,219), and ANGST consortium (n = 17,310, and n = 18,186).\n\nMain outcome measuresAN diagnosis, worry, anxiety disorder pathology (case-control and quantitative phenotypes).\n\nResultsWe found evidence of a moderate genetic correlation between worry and AN (Rg = 0.36, SE = 0.05, p < 0.001), and the Mendelian randomization analysis supported a causal influence of worry on AN (OR = 2.14, 95% CI: 1.18 to 3.90, p = 0.01). There was no clear evidence for a causal effect of AN on worry in this study (B = -0.01, 95% CI: -0.03 to 0.02, p = 0.55). There was no robust evidence for a causal influence of anxiety disorders on AN (for case-control anxiety disorder phenotype: OR = 1.02, 95% CI: 0.69, 1.50, p = 0.922; for quantitative anxiety disorder phenotype: OR = 4.26, 95% CI: 0.49, 36.69, p = 0.187). There was no robust evidence for a causal effect of AN on anxiety disorders (for case control anxiety disorder phenotype: OR = 1.00, 95% CI: 0.72, 1.38, p = 0.981; for quantitative anxiety disorder phenotype: B = 0.01, 95% CI: -0.06, 0.6=09, p = 0,761). AN and anxiety disorder phenotypes were not genetically correlated (for case-control anxiety disorder phenotype: Rg = 0.10, se = 0.17, p = .56; for quantitative anxiety disorder phenotype: Rg = 0.12, SE = 0.17, p = 0.47).\n\nConclusionsFindings support a role for worry in AN development, highlighting a potential target of future AN prevention efforts. Mechanisms underlying the association should be a focus of future investigation. The relatively small sample sizes of anxiety disorder and AN GWASs may have limited power to detect causal effects; these associations should be studied further.

epidemiology↗